Author(s)

M. Echávarri de Miguel, C. Varela Guisasola, A. Sánchez Alonso, A. Abril Cabero, E. Nieto Martil, A. Merino Pardo, E. Algarra Sánchez, B. Riva de la Hoz, B. Márquez Arce, B. Leal Pino, M. Pozas del Río

Why was it done?

Lactose used as a pharmaceutical excipient is generally obtained from skimmed milk and purified to remove milk proteins. Pharmacopoeias specify that lactose must be free from protein contaminants; hence, it has been considered safe for patients with cow’s milk protein allergy (CMPA). However, in severe allergies, medicines containing natural lactose should be avoided due to the potential risk of protein contamination. Although rare, cases of anaphylaxis from contaminant milk proteins have been reported, particularly with dry-powder inhalers, injectables, and vaccines.
This initiative arose after a suspected allergic reaction in a patient with severe CMPA following administration of an injectable containing lactose as an excipient. Given limited evidence and lack of transparency about lactose origin, an internal guideline was developed to enhance patient safety.

What was done?

An internal hospital guideline was developed and implemented to verify the origin—natural or synthetic—of lactose used as an excipient in medicines. The guideline was created through systematic screening assisted by artificial intelligence, followed by verification with manufacturers.

How was it done?

With ChatGPT support, a Python-based code was created to analyze 3,278 pharmaceutical specialties for the presence of lactose. Manual validation of 360 medicines (95% confidence level, ±5% margin of error) confirmed the method’s reliability. The most dispensed medicines and all intravenous formulations, vaccines, and inhalers were reviewed due to higher risk described in literature. Manufacturers were contacted to determine whether lactose was natural or synthetic. Main challenges included delayed responses and limited data due to confidentiality.

What has been achieved?

Of the 3,278 medicines analyzed, 350 contained lactose or mentioned it in their product information, 1,522 did not, and 1,406 were inactive codes. Lactose origin was investigated for 152 products from 58 manufacturers, with responses in 92 cases (60.5%). Only five (5.4%) contained synthetic lactose. High-risk medicines included one inhaler and eight injectables (two vaccines) with natural lactose. Manual validation showed 100% concordance with automated results.

What next?

Next steps include expanding data to over 350 confirmed medicines, publishing results for open access, and developing an app for healthcare professionals. Integration into prescribing and dispensing systems is planned to generate automatic alerts for patients with severe CMPA.

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Author(s)

G. Penocchio, F. Bertola, F. Bozza, F. Caravaggio, M. Ferrighi, M.P. Ghilardi, A. Pozzi, G. Trainini, C. Galloni, T.E. Testa.

Why was it done?

Epidermolysis bullosa (EB) comprises a group of rare disorders with multisystem effects. In the postnatal period, a 37-week -old infant presented with dysepithelialized lesions on the body, as well as involvement of the oral cavity, characterized by discoloration of the hard palate and gums. The multidisciplinary team diagnosed EB and deemed it necessary to apply lidocaine gel because the infant was unable to feed due to pain from the sores. Initially, several commercially available products were used, but their irritating excipients led to poor tolerance. Consequently, it was necessary to prepare an extemporaneous formulation devoid of preservatives and flavorings.

What was done?

This intervention presents the development of an extemporaneous preparation of lidocaine hydrochloride 0.5% w/w viscous oral topical gel, free of preservatives and flavors. The gel was distributed to the neonatal intensive care unit staff in pre-filled syringes and applied to the oropharyngeal mucosa of a neonate diagnosed with EB.

How was it done?

The components of the preparation included lidocaine hydrochloride, carboxymethylcellulose sodium (CMC), and sterile water. CMC was chosen for its hydrophilic properties and excellent gelling capabilities. The gel was prepared using a high-shear magnetic stirrer, with increasing concentrations of CMC (0.75%, 2.25%, 3%, and 4%). After discussions with the multidisciplinary team, the pharmacist recommended using the 4% gel, as its density allowed it to adhere well to the oropharyngeal mucosa. This adherence is crucial for preventing absorption and minimizing potential cardiac side effects of lidocaine.

What has been achieved?

The gel was successfully prepared with 0.5% lidocaine and 4% CMC, and packaged in pre-filled syringes with the daily dosage. Due to the absence of preservatives and stability data, the shelf life was established at 15 days when stored at 2-8°C. The viscous oral gel was administered three times a day, 20 minutes before feeding, to exert its anesthetic effect and facilitate breastfeeding.

What next?

The hospital pharmacist’s extensive expertise was instrumental in determining the optimal concentration of CMC and customizing the formulation to meet the patient’s unique requirements. This pivotal contribution led to a highly personalized therapy, ultimately resulting in the successful discontinuation of artificial nutrition in this critically ill patient.”